title: Notch and NF-κB signaling pathways in the biology of classical Hodgkin lymphoma.
abstract: Classical Hodgkin lymphoma (cHL) is now recognized as a B-cell-derived lymphoma which is characterized by only about 1% malignant pathognomonic Hodgkin and Reed-Sternberg (HRS) cells and an abundant infiltrate of reactive bystander cells. HRS cells are unique with respect to their lost B-cell-specific gene expression pattern and recurrent genetic lesions. Aberrant activity of Notch signaling, a highly conserved developmental pathway, acts as a negative regulator of the B cell program in HRS cells and thereby contributes to their reprogramming. Another striking feature and the major pathogenetic mechanism in HRS cells is constitutive NF-κB activation. A number of aberrations that contribute to canonical NF-κB activity in HRS cells have been described such as genetic lesions, deregulated receptor signaling and Epstein-Barr virus (EBV) infection. The importance of Notch and NF-κB signaling for cHL pathogenesis, their potential cross-talk and implications for future therapeutic applications are being discussed.
authors.affiliation: Department of Hematology and Oncology, Charité, Campus Virchow-Klinikum, University Medicine Berlin, 13353 Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schwarzer
authors.forename: F
authors.initials: F
authors.lastname: Jundt
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D016393:Lymphoma, B-Cell; D016328:NF-kappa B / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D051880:Receptors, Notch